TY - JOUR
T1 - RFC1 expansions are a common cause of idiopathic sensory neuropathy
AU - Currò, Riccardo
AU - Salvalaggio, Alessandro
AU - Tozza, Stefano
AU - Gemelli, Chiara
AU - Dominik, Natalia
AU - Galassi Deforie, Valentina
AU - Magrinelli, Francesca
AU - Castellani, Francesca
AU - Vegezzi, Elisa
AU - Businaro, Pietro
AU - Callegari, Ilaria
AU - Pichiecchio, Anna
AU - Cosentino, Giuseppe
AU - Alfonsi, Enrico
AU - Marchioni, Enrico
AU - Colnaghi, Silvia
AU - Gana, Simone
AU - Valente, Enza Maria
AU - Tassorelli, Cristina
AU - Efthymiou, Stephanie
AU - Facchini, Stefano
AU - Carr, Aisling
AU - Laura, Matilde
AU - Rossor, Alexander M
AU - Manji, Hadi
AU - Lunn, Michael P
AU - Pegoraro, Elena
AU - Santoro, Lucio
AU - Grandis, Marina
AU - Bellone, Emilia
AU - Beauchamp, Nicholas J
AU - Hadjivassiliou, Marios
AU - Kaski, Diego
AU - Bronstein, Adolfo M
AU - Houlden, Henry
AU - Reilly, Mary M
AU - Mandich, Paola
AU - Schenone, Angelo
AU - Manganelli, Fiore
AU - Briani, Chiara
AU - Cortese, Andrea
N1 - © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2021/5/9
Y1 - 2021/5/9
N2 - After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies.
AB - After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies.
U2 - 10.1093/brain/awab072
DO - 10.1093/brain/awab072
M3 - Article
C2 - 33969391
JO - Brain
JF - Brain
SN - 0006-8950
ER -